1. Field of the Invention
This invention relates to a new process for particle fractionation. More particularly, the invention relates to a new process for the separation of particles or molecules according to size or to other physical characteristics, and to a new type of apparatus for accomplishing the same.
Specifically, the invention provides a new continuous process for separation of particles which gives a surprising and unexpected increase in the resolution and speed of separation compared to known methods. The new process broadly comprises continuously introducing two or more fluid substreams of different composition into separate inlet ports of a thin enclosed channel having an inlet and outlet end and having a thickness which is very thin compared to the other two dimensions and bringing the substreams into contact with adjacent substreams so as to collectively form a series of thin laminae flowing parallel to one another within the channel and in contact with one another over a sufficient length of channel to allow a desired level of mass transport between and through laminae without substantial hydrodynamic mixing between the laminae, continuously introducing a fluid medium containing the particles to be separated as one or more of the fluid substreams and independently of the particle concentration, varying the fluid composition of the different substreams as needed to realize separation, at the outlet end of the channel splitting the collective stream into another set of substreams so as to permit separate recovery of one or more of the substreams at the outlet end of the channel, continuously removing all of the substreams flowing from the outlet ports at the outlet end of the channel, and during the separation process occuring in the channel subjecting the channel to a special transverse driving force or gradient described hereinafter having a component perpendicular to the flow plane within the channel.
As a special embodiment, the invention provides a process for separation of particles using two or more of the above-noted channels in linked array or series wherein the channels are joined by fluid streams in which one or more of the outlet substreams from 1 channel or cell is fed to 1 or more of the inlet substreams of another cell or of more than one other cell.
The invention further provides a new type of separation apparatus or cell for use in the above-noted process which comprises one or more special split flow thin separation cells which permits one to effect the above-noted rapid and efficient separation or fractionation of particles.
2. Prior Art
There is a growing need in industry for the separation of particles including both cell-size particles and those of submicron and macromolecular size, such as various viruses, latices and polymers. Various methods have been proposed, but in general, they have been too slow, too low in throughput, inefficient, expensive or have failed to effect the separation with the desired degree of resolution needed for commerical operations.
Some of the highest resolution techniques disclosed have been those based on field-flow fractionation as disclosed in U.S. Pat. Nos. 3,449,938, 4,147,621 and 4,250,026. Other references include Giddings, Anal. Chem. 57 945 (1983). and Giddings et al-Sep. Science and Tech. 18 (3) 293-306 (1983). These prior known methods, however, are limited in throughput as they are batch techniques that do not operate normally on a continuous basis. They are designed as analytical-scale techniques and they fail to resolve adequate quantities of material needed for many applications.
The prior known methods thus present a critical defect in meeting the needs of industry. The increasing competitiveness of industry and the rapid evolution of new technologies is now putting extraordinary demands on separation process. Many industrial processes require that many particulate and macromolecular materials be processed in a way that produces homogeneous fractions of narrow size distribution. Where separation processes are used to produce these materials, the processes must have a relatively high throughput so that the required amount of material can be processed. In addition, the operation is preferably made as simple as possible. Continuous separation processes are desirable both from the point of view of simplicity of operation and the ability to process large quantities of materials.
This demand for effective preparative methods are particularly stringent in a rapidly growing area of biotechnology. Here the resolution must be high in order to remove a plethora of unwanted (and in some cases hazardous) contaminants from the products, and yet the processes must be simple enough and provide adequate throughput for economic viability. In biotechnology there is one additional demand; the separative processes must often occur rapidly so that sensitive biological species are not long removed from their normal stable environments.
There is thus a rapidly growing need for new separation technology for which the througput is continuous, the resolution is high, and the separation is fast. In addition, because of the enormous variety of separation needs, the separation process should preferably be based on as large a variety of molecular and particulate properties as is possible.
The unexpected superior results obtained by the present process as compared to the prior known techniques, such as field flow fractionation, are shown in Example II. As shown therein even by using a smaller cell volume and lower concentrations of solids in the feed suspension, the present process achieves a rapid throughput some 1400 times greater than that achieved in the field-flow fractionation technique. In addition, the process gives excellent resolution, is fast and uses simple equipment, and clearly meets the needs of industry as noted above.
It is an object of the invention, therefore, to provide a new and efficient process for particle fractionation. It is a further object to provide a new process for separation of particles from fluid media which can be accomplished in a rapid and efficient manner. It is a further object to provide a new process for particle fractionation which permits high resolution of separation. It is a further object to provide a process for separation of particles from fluid media which can be operated in a continuous manner. It is a further object to provide a new process for particle fractionation which permits separation on a single pass through the apparatus. It is a further object to provide a new separation process for particles which is economical to operate and uses inexpensive equipment. It is a further object to provide a new type of separation channel or cell which can be operated singly or in combination with other cells. It is a further object to provide a new split flow thin separation cell which gives superior unexpected results in the separation of particles. These and other objects will be apparent from the following detailed description thereof.